Reglan / Metoclopramide

In an unpublished opinion file on April 9, the Court of Appeals for the 5th Circuit affirmed a previous decision in one of the Reglan generics cases, Whitener v. Pliva, Inc. This ruling upholds the district court’s grant of summary judgment in favor of the defendant drug companies on the grounds that the defendants performed no off-label promotional activities.

Lindsey and Joshua Whitener’s son was born prematurely and with severe birth defects after Mrs. Whitener used metoclopramide, a generic form of the heartburn drug Reglan. Mrs. Whitener was suffering nausea and morning sickness and her doctor, Dr. John McCrossen, prescribed metoclopramide as an off-label treatment due to previous successes he’d had with the drug.

The FDA-approved label did not mention any warnings regarding used during pregnancy nor did it recommend metoclopramide as a treatment for pregnancy-related nausea. The Whiteners filed suit in 2010 alleging that the drug’s manufacturers failed to warn them of the danger of using their product during pregnancy and also that the manufacturers had engaged in a “complex scheme” of promotion of the off-label use.

Of the six defendants, three were manufacturers of brand name Reglan (Alaven Pharmaceutical L.L.C., Meda Pharmaceuticals, Inc. and Schwarz Pharma, Inc.), which Mrs. Whitener did not use. The other three (PLIVA, Inc., Barr Laboratories, Inc. and Teva Pharmaceutical Industries, Ltd.) made generic metoclopramide, which Mrs. Whitener did use.

A 2011 U.S. Supreme Court ruling in PLIVA, Inc. v. Mensing, held that state law inadequate warning claims against generic drug manufacturers were preempted, as federal law required the generic labels to be the same as the brand name labels. The 5th Circuit granted defendants’ motions for judgment on the pleadings in the matter of the inadequate warnings. However, it allowed the claim of promotion of off-label use to proceed.

Teva was released from the case due to a jurisdictional issue. The remaining defendants moved for summary judgment on the grounds that the Whiteners could not prove that the premature birth and birth defects were directly caused by any off-label promotion in which they may have engaged. The Whitener’s own doctor, Dr. McCrossen, provided the testimony the court needed to support the motion for summary judgment.

In Dr. McCrossen’s testimony, he stated unequivocally that the decision to prescribe metoclopramide was mad based on his “clinical experience” that the drug “works good to control nausea and vomiting associated with pregnancy.” He further testified that he had never spoken to a representative of the defendants regarding the drug, nor had he been given samples. To the best of his knowledge, no one in his practice had had contact with the defendants either.

Under the court’s Rule 47.5.4, this unpublished opinion is not precedent “except under the doctrine of res judicata…, etc. An unpublished opinion may be cited pursuant to Fed. R. App. P. 32.1(a).” This does not bode well for other plaintiffs with similar claims.

Lawsuits over the drug Reglan (Metoclopramide) fascinate me because of the unique nature of the disorders the drug can cause. Reglan can cause movement disorders like tardive dyskinesia. Individuals suffering from these disorders lose control of their facial muscles and their limbs. It’s incredibly strange to me that temporary use of this drug can cause someone to permanently develop movement disorders.

Below you’ll find an assortment of documents filed in Reglan lawsuits from around the country. If you’d like me to put you in touch with a Reglan lawyer, feel free to email me at justinian at justinian dot us, or use the form to the right.

Metoclopramide is the generic version of Reglan. New evidence has shown that individuals who use Reglan for 12 or more weeks are at a greater risk of developing a movement disorder such as tardive dyskinesia. Here’s the excerpt of a lawsuit filed against a Metoclopramide manufacturer:

23. The package inserts for metoclopramide products, and the PDR monograph for Reglan, contained false and/or misleading statements and omitted information material to the foreseeable and ordinary contemplated uses of the products. These statements and omissions include:

a) The statement that “Like the phenothiazines and related drugs, which are also dopamine antagonists, metoclopramide produces sedation and may produce extrapyramidal reactions, although these are comparatively rare (See WARNINGS).” This statement is false and misleading in light of the manufacturers' knowledge that extrapyramidal reactions are far more common, particularly when metoclopramide is used long-term and their concurrent knowledge that metoclopramide is commonly prescribed for long-term use.

The new website is www.findtherightreglanlawyer.com. If you or someone you know has developed a movement disorder and ever took Reglan or Metoclopramide, check the site out. Perhaps I can help connect you with the right lawyer to handle your case.

This memo from Health and Human Services was produced during the discovery process of a Metoclopramide lawsuit. The memo was filed with the court in 2005, so it presumably is older than that.

The Division of Neuropharmacologic Drug Products requested an AERS review of cases of movement disorders and neuroleptic malignant syndrome relating to metoclopramide use. Myzan (formerly MT 100) a combination of naproxen sodium (500 mg) and metoclopramide (16 mg), is being considered for approval for the indication of acute treatment of migraine (intermittent dosing). To characterize these possible movement disorders related to metoclopramide use, AERS cases that were coded with the following movement disorders were retrieved and analyzed: tardive dyskinesia, metoclopramide-induced Parkinsonism, akathisia, and acute dystonia. A total of 401 cases were included in the analysis.

The characteristics of the 401 cases retrieved from the AERS database involving movement disorders and NMS related to metoclopramide use reinforce what has been shown in the literature and product labeling regarding these adverse events. For the most part, the movement disorders are reversible over time. Unfortunately, some patients continue to have symptoms or recover with sequelae after the drug has been discontinued; most of these cases are associated with chronic (>30 days) therapy with metoclopramide.

This lengthy report explains the regulatory and clinical history of Reglan and Metoclopramide, including their association with movement disorders:

My testimony will include discussion regarding enumerable published reports, that have been accumulating since 1978, that evidence that CAPs are strongly associated with Tardive Dyskinesia (hereafter TD) when given at sufficient dose for a sufficiently long duration (i.e., duration of exposure is a major risk factor for CAP-induced TD). The term “Tardive Dyskinesia” is used to describe all persistent, occasionally reversible, abnormal movements caused by prolonged exposure to dopamine antagonists. The most common form of TD presents as orofacial stereotypy (i.e., involuntary, repetitive oral facial and lingual movements that resemble chewing, lip smacking, tongue protrusion), at times associated with choreatic movements (i.e., brief, irregular contractions that are not repetitive or rhythmic, but appear to flow from one muscle to the next) of the extremities and trunk (Jimenez-Jimenez, 1997).

Apparently, movement disorders have been known side effects of Reglan and Metoclopramide for over thirty years. Scary.

One of the claims made in most Reglan or Metoclopramide lawsuits is that the manufacturer of the drug failed to adequately warn the plaintiff of the risks of using the drug. (One of the risks of using Reglan or Metoclopramide is developing a movement disorder; Tardive Dyskinesia is a known side-effect of Reglan use.)

The Reglan lawyers who represent the manufacturers of the drugs often argue that even if the warning label left something out, all that matters is that the manufacturer complied with the FDA regulations. This is a very hotly contested issue that will probably be before the Supreme Court by 2011.

That said, here’s the report of one expert who believes that Teva appropriately labeled its generic Reglan product.

A. Metoclopramide, as a prescription drug marketed under an FDA-approved New Drug Application (NDA) has undergone rigorous scientific testing and evaluation for its efficacy and safety for use in the treatment of an assortment of digestive disorders. Further, It can only qualify as a pharmaceutical for therapeutic use if it has been appropriately labeled and properly manufactured, as required by the FDA regulations for approval of new drug products.

Pharmaceutical prescription drugs that are approved for marketing in the U.S. have been the subject of a rigorous program of scientific testing and evaluation that is required by the regulations of the U.S. Food & Drug Administration under the Food, Drug and Cosmetic Act.

This program includes in vitro testing, toxicology studies in multiple animal species and three phases of clinical testing that typically involve carefully controlled studies in thousands of patients to demonstrate that a pharmaceutical is safe and effective for human use. These steps are described in regulations that outline the different tests that are required to establish the efficacy and safety of a drug product (21 C.F.R. §312.21).

Steven Lamm, M.D., DTPH, gave the following expert report in a Reglan lawsuit. The report establishes that some people who used Reglan or Metoclopramide for over 12 weeks developed movement disorders such as Tardive Dyskinesia.

"The literature on tardive dyskinesia and Metoclopramide begins with case reports and reports of case series. These reports demonstrate an association between metoclopramide and tardive dyskinesia but do not provide a quantitative estimate of risk.

Medical records that report drug use and pharmacy records have been used to describe the population characteristics of metoclopramide users, but without reports of tardive dyskinesia cases, they are unable to provide risk estimates.

The first data that do yield an initial estimate of risk come from national adverse drug reaction registries in which reported cases of tardive dyskinesia in metoclopramide patients have been compared with drug sales data.

Cross-sectional studies report the prevalence of signs of tardive dyskinesia among metoclopramide users, but without a time factor that would allow an assessment of the frequency of the development of tardive dyskinesia, they do not provide a basis for calculating the risk.

Clinical studies in which patients placed onto metoclopramide have been followed over time during which the development of tardive dyskinesia can be observed would provide a basis for calculating the risk of acquiring tardive dyskinesia. These observations are generally found within data submitted to the drug regulatory agencies and not specifically in the published literature."

This report is a little outdated, as newer evidence has found a much clearer link between movement disorders and Reglan.

One of the things a plaintiff in a Reglan lawsuit will almost always have to prove is which manufacturer’s version of Reglan or Metoclopramide the plaintiff took. While all versions of Metoclopramide have the same side effects, that usually isn’t enough to hold manufacturer A liable for injuries caused by manufacturer B’s product.

Good Metoclopramide lawyers know how to find out which brand of the drug that the plaintiff took. However, sometimes things don’t work out as planned:

10. The Food and Drug Administration (FDA) Center for Drug Evaluation and Research maintains a National Drug Code Directory (NDC Directory) that serves as a universal product identifier for prescription drugs. Each prescription drug product listed under Section 510 of the Federal Food, Drug and Cosmetic Act is assigned a unique number, called its National Drug Code (NDC) number. 21 CFR 207.35, (App. at 134-136).

11. The NDC number “00031-6701-63” was assigned to brand name Reglan(R) 10mg tablets manufactured by Wyeth. (Affidavit of Dwayne Clark Custodian of Pharmacy Records for SUPERVALUE INC., at 3, App. at 139).

12. The NDC number associated with prescription No. 6414839 is not assigned to Schwarz. ( Id. at 4) Instead, Schwarz' NDC number for Reglan 10mg tablets, after December 27, 2001 when Schwarz acquired the rights to Reglan(R), was “00091-6701-63.” ( Id.).

13. The inclusion of the “SCHWZ” notation on prescription No. 6414839 was an error in the Albertson's Sav-On Pharmacy ASDRx records; this error occurred during the company's conversion from the Zadall database to the ADSRx database, when data regarding manufacturer numbers was supplied by First Data Bank. ( Id. at 2-3, 4-5, App. at 138-141). When First Data Bank mistakenly associated the NDC number “00031-6701-63” (which is assigned to Wyeth) with Schwarz, the abbreviated name “SCHWZ” was automatically, and erroneously, substituted for Wyeth in the manufacturer field for the ADSRx database. ( Id. at 4-5, App. at 140-141).

If you need help determining which brand of Reglan or Metoclopramide you took, don’t hesitate to contact me. I’d love to help you identify the product manufacturer and point you to a good lawyer.

The lawyers for Wyeth and Schwarz filed this motion for summary judgment in Nevada. One of the issues raised is whether Wyeth, as the firm that first brought Reglan to market, can be held liable if someone is injured while taking Metoclopramide, the generic form of Reglan.

People who have used Metoclopramide or Reglan for longer than 12 weeks are at risk of developing movement disorders like Tardive Dyskinesia. Movement disorders are known Reglan side effects.

About this Blog

This blog chronicles legal and scientific news relating to personal injuries caused by defective drugs and medical devices. It is published by injury lawyer Justinian C. Lane, an attorney who takes a personal interest in each of his clients’ cases.